The process is divided into three main stages: antigen recognition, SMAC formation and effector function, and TCR-pMHC disengagement. The diagram is further broken down into three detailed sections: catch bond formation, contact stabilization, and cytotoxic function. In catch bond formation, the target cell interacts with the T cell through various molecules like CD80/86, CD28, CD4/8, CD45, and LAT. The T cell has components such as LCK and ZAP70. In contact stabilization, molecules like VCAM-1 and ICAM-1 interact with inactive and active forms of VLA-4 and LFA-1. The diagram shows the distribution of forces indicated by F symbols. In cytotoxic function, perforin and granzyme are released towards the target cell. The bottom left inset shows a detailed view of the TCR:pMHC interaction, highlighting components like MHC, TCR, CD3, and the FG loop. The bottom right inset shows the organization of the immunological synapse with regions labeled as pSMAC and dSMAC.
Mechanobiology of T-cell activation and cytotoxic function. T cells form transient exploratory contacts before antigen recognition. Upon engagement with cognate pMHC, the TCR experiences mechanical forces that are transmitted to CD3 subunits, initiating signaling and promoting CD45 exclusion from the contact site. Integrins such as LFA-1 and VLA-4 switch to their high-affinity conformations to stabilize the interface and couple external forces to the actin cytoskeleton. Actin polymerization and retrograde flow organize the IS and reinforce signaling. During cytotoxic responses, contractile and compressive forces, together with elevated membrane tension at the synapse, support the targeted release of perforin and granzymes. Red âFâ symbols indicate regions where mechanical forces are particularly important.